Development of animal models with chronic kidney disease-mineral and bone disorder based on clinical characteristics and pathogenesis.

Journal and index pages often block iframe embedding. This reader keeps the evidence details in Orthonotes and leaves the source page one click away.

Abstract

[Indexed for MEDLINE] Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 5. J Cell Mol Med. 2020 May;24(9):4931-4943. doi: 10.1111/jcmm.14991. Epub 2020 Apr 11. Mutational landscape and genetic signatures of cell-free DNA in tumour-induced osteomalacia. Wu N(1)(2)(3), Zhang Z(1)(2), Zhou X(1), Zhao H(1)(4), Ming Y(5), Wu X(6), Zhang X(7), Yang XZ(8), Zhou M(4), Bao H(6), Chen W(1)(2)(9), Wu Y(7), Liu S(1)(2)(3), Wang H(8), Niu Y(8), Li Y(10), Zheng Y(11), Shao Y(7), Gao N(1), Yang Y(1), Liu Y(1), Li W(1), Liu J(1), Zhang N(1), Yang X(1), Xu Y(1), Li M(12), Sun Y(13)(14), Su J(4), Zhang J(1)(2)(3), Xia W(12), Qiu G(1)(2)(3), Liu Y(1), Liu J(1)(2)(15), Wu Z(2)(3)(8). Author information: (1)Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. (2)Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China. (3)Key laboratory of big data for spinal deformities, Chinese Academy of Medical Sciences, Beijing, China. (4)School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China. (5)PET-CT Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. (6)Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON, Canada. (7)Nanjing Geneseeq Technology Inc., Nanjing, China. (8)Department of Central Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. (9)Graduate School of Peking Union Medical College, Beijing, China. (10)Department of Breast Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. (11)Beijing Ekitech Co. Ltd., Beijing, China. (12)Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. (13)Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. (14)University of Chinese Academy of Sciences, Beijing, China. (15)Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Tumour-induced osteomalacia (TIO) is a very rare paraneoplastic syndrome with bone pain, fractures and muscle weakness, which is mostly caused by phosphaturic mesenchymal tumours (PMTs). Cell-free DNA (cfDNA) has been regarded as a non-invasive liquid biopsy for many malignant tumours. However, it has not been studied in benign tumours, which prompted us to adopt the targeted next-generation sequencing approach to compare cfDNAs of 4 TIO patients, four patients with bone metastasis (BM) and 10 healthy controls. The mutational landscapes of cfDNA in TIO and BM groups were similar in the spectrum of allele frequencies and mutation types. Markedly, deleterious missense mutations in FGFR1 and loss-of-function mutations in MED12 were found in 3/4 TIO patients but none of BM patients. The gene ontology analysis strongly supported that these mutated genes found in TIOs would play a potential role in PMTs' process. The genetic signatures and corresponding change in expression of FGFR1 and FGF23 were further validated in PMT tissues from a test cohort of another three TIO patients. In summary, we reported the first study of the mutational landscape and genetic signatures of cfDNA in TIO/PMTs. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. DOI: 10.1111/jcmm.14991 PMCID: PMC7205804